Proteoglycans (PG) are integral components of the connective tissue matrix of a variety of tissues. Historically, these protein-carbohydrate macromolecules have been considered inert structural components of these tissues, having no function in cell or tissue metabolism. However, within the past several years these biomolecules have been seen to play a dynamic role in the normal and pathogenic functions of tissues and cells. In the aorta, the concentration of the carbohydrate component of the proteoglycan, the glycosaminoglycans (GAG), has been positively correlated with cardiovascular disease (specifically atherosclerosis) and with the cholesterol content of the vessel. Proteoglycans have been shown to bind to plasma low-density lipoproteins (LDL) in vitro. This fact is the basis for the theory concerning the initiation and progression of atherosclerosis. Fewer investigations have been conducted concerning the biochemical structure and role of these connective tissue macromolecules in normal and diseased corneal tissue. However, many questions still remain concerning the identity, structure, synthesis, and general metabolism of the proteoglycans of the extracellular matrix. This proposal addresses the structural and functional analyses of proteoglycans isolated from normal and pathogenic aortic and ocular tissue. Using gel filtration, ultracentrifugation and ion-exchange techniques PG are to be purified: 1) from arterial vessels with differing susceptibility to atherosclerosis, 2) from atherosclerosis-prone sites and areas which remain plaque-free in a given vessel, 3) from the same vessel(s) (from frozen samples) in two strains of pigeons differing in their susceptibility to atherosclerosis, 4) from normal and diseased human corneal tissue, and 5) from human scleral tissue. These PG and their component GAGs and protein cores, are to be evaluated structurally and their in vitro binding to plasma LDL examined. Fresh tissue is to be incubated with 35-S sodium sulfate in an organ culture system to investigate PG synthesis and metabolism in these tissues. By investigating the structural and functional differences of PG purified from different sources information concerning the role of PG in atherosclerosis and diseases causing corneal opacity can be ascertained. Simultaneous with these goals is the training of minority scientists in the biomedical sciences.